Neuronal growth factors, neurotrophins and memory deficiency

Abstract

CNS and PNS ontogenesis are regulated by various proteic factors, and the best characterized of which still remains Nerve Growth Factor (NGF), a molecule exerting trophic, tropic (i.e. directing growing axons toward NGF-releasing target tissue) and differentiative effects on a number of neural and non-neural (e.g. mast-cells) cell lines. Other Growth Factors (GFs), called ‘neurotrophins’ (BDNF, NT-3, NT-4, NT-5) also exert similar effects on specific neural cell population. Other GFs (EGF, TGFs, IGFs, FGFs) share these growth-promoting properties with the neurotrophins. NGF appears to regulate specifically the postnatal maturation of the CNS cholinergic in altricial rodents. In adults, cholinergic neurons show retrograde transport for NGF and degeneration of cholinergic neurons after fimbria-fornix transection is prevented by NGF infusion, suggesting a role for NGF in maintaining normal cholinergic function in adulthood. However, peptidergic neurons (e.g. SP-positive cells) seem also to be influenced by perinatal NGF administration, indicating that the spectrum of NGF actions is wider than previously reported. In recent years we investigated the role of NGF in controlling behavioural maturation in the early postnatal period by comparing NGF effects with those of related and non-related neurotrophins (EGF, basic FGF, IGF-1, Transforming GF-alfa). We found that a single intracerebral injection of NGF accelerates cholinergic maturation on postnatal day (PND) 20, as shown by the enhanced reactivity to the muscarinic blocker scopolamine. Scopolamine-induced hyperactivity, normally appearing at the end of the third week, emerges already at PND 5 following NGF administration on PND 2 and 4. Learning and retention capabilities are alos influenced by intracerebral NGF in a passive avoidance task (PND 11–12). In the latter, sequestration of endogenous NGF by NGF-antibody administration prevents the 24-h retention normally present on PND 15.